Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

Pei

Journal of Immunology Research

et al. 2015

Objective. To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. Methods. Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC) curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. Results. The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI): 6.0%–15.0%) and 99.0% (95% CI: 98.0%–100.0%). The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA) subtype (48.0%; 95% CI: 31.0%–65.0%) than in the other subtypes (17.0%; 95% CI: 14.0%–20.0%) and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%–20.%%) than the other assays (0.05%; 95% CI: 2.0%–11.0%). Conclusions. Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Meta-Analysis: Diagnostic Accuracy of Anti-Cyclic Citrullinated Peptide Antibody for Juvenile Idiopathic Arthritis

Pei

Journal of Immunology Research

et al. 2015

Journal of Neurosurgery

“…This would be in keeping with the action of IL-1Ra in other inflammatory disease states, such as juvenile rheumatoid arthritis, where anakinra has an established therapeutic use and where fibrinogen levels correlate with disease activity. 12 Fibrinogen levels, in addition to CRP platelet activation, have been previously demonstrated to be associated with worse outcomes following aSAH. 10 Although we have no evidence that IL-1Ra improves outcome by reducing fibrinogen levels, it is nevertheless reassuring that in our study, anakinra reduces a number of inflammatory markers that have been associated with poor outcomes following aSAH.…”

Section: Table 2 the Mean Plasma Concentrations Of Il-6 Crp Il-8 mentioning

confidence: 99%

Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study

Galea

Ogungbenro²,

Hulme

et al. 2018

OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH. Its effects are attenuated by its naturally occurring antagonist, IL-1 receptor antagonist (IL-1Ra [anakinra]). The authors hypothesized that administration of additional subcutaneous IL-1Ra would reduce inflammation and associated plasma markers associated with poor outcome following aSAH. METHODS This was a randomized, open-label, single-blinded study of 100 mg subcutaneous IL-1Ra, administered twice daily in patients with aSAH, starting within 3 days of ictus and continuing until 21 days postictus or discharge from the neurosurgical center, whichever was earlier. Blood samples were taken at admission (baseline) and at Days 3-8, 14, and 21 postictus for measurement of inflammatory markers. The primary outcome was difference in plasma IL-6 measured as area under the curve between Days 3 and 8, corrected for baseline value. Secondary outcome measures included similar area under the curve analyses for other inflammatory markers, plasma pharmacokinetics for IL-1Ra, and clinical outcome at 6 months. RESULTS Interleukin-1Ra significantly reduced levels of IL-6 and C-reactive protein (p < 0.001). Fibrinogen levels were also reduced in the active arm of the study (p < 0.002). Subcutaneous IL-1Ra was safe, well tolerated, and had a predictable plasma pharmacokinetic profile. Although the study was not powered to investigate clinical effect, scores of the Glasgow Outcome Scale-extended at 6 months were better in the active group; however, this outcome did not reach statistical significance. CONCLUSIONS Subcutaneous IL-1Ra is safe and well tolerated in aSAH. It is effective in reducing peripheral inflammation. These data support a Phase III study investigating the effect of IL-1Ra on outcome following aSAH. Clinical trial registration no.: EudraCT: 2011-001855-35 ( www.clinicaltrialsregister.eu ).

“…Fibrinogen is the principal protein responsible for blood clotting in vertebrates and its major function is as the precursor to fibrin. Fibrin also plays a key role in the inflammatory response (Gilliam et al , 2011). The different expression levels of fibrinogen C domain-containing protein 1-B, partial, fibrinogen-like protein 1-like and fibrinogen-like protein A in A. japonicus under low DO conditions might indicate a disordered immune defence system.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of gene expression profile in the respiratory tree of sea cucumber (Apostichopus japonicus) in response to hypoxia conditions

Zhang¹,

Feng²,

Ding³

et al. 2017

J. Mar. Biol. Ass.

The sea cucumber Apostichopus japonicus is a deposit-feeder and vital for marine benthic ecosystems. Hypoxia can influence the behaviour and even lead to massive mortality in A. japonicus in the wild. It is important to understand the molecular responses of A. japonicus when exposed to acute changes in dissolved oxygen (DO) concentration. In this study, RNA-seq provided a general overview of the gene expression profiles of the respiratory tree of A. japonicus exposed to DO of 8 mg l−1 (DO8), 4 mg l−1 (DO4) and 2 mg l−1 (DO2) conditions. Differentially expressed genes (DEGs) screening with the NOISeq method identified 51, 59 and 61 DEGs according to the criteria of fold change ≥2 and divergence probability ≥0.8 in the comparisons of DO2 vs DO4, DO2 vs DO8 and DO4 vs DO8, respectively. Gene ontology analysis showed that ‘cellular process’ and ‘binding’ had the most enriched DEGs in the categories of ‘biological process’ and ‘molecular function’, respectively (catalytic activity also had the most enriched DEGs in the category of ‘molecular function’ based on the comparison of DO2 vs DO8), while ‘cell’ and ‘cell part’ had the most enriched DEGs in the category of ‘cellular component’. The DEGs were mapped to 79, 81 and 104 pathways in the KEGG database, and 8, 29 and 16 pathways were significantly enriched, respectively. The DO-specific DEGs identified in this study of the respiratory tree are important targets for further research into the biochemical mechanisms involved in the response of the sea cucumber to changes in the DO concentration.